Abstract Chronic obstructive pulmonary disease (COPD) is a growing cause of morbidity and mortality around the world in countries of all levels of economic prosperity. COPD is a complex disorder characterized by permanent airway ?ow obstruction that interferes with normal respiration. Imaging-based biomarkers are of increasing importance in our search to identify COPD phenotypes, establishing homogeneous sub-populations to aid in genotyping, and directing therapeutic interventions and associated outcomes assessment. Computed tomography (CT) imaging can describe the spatial distribution of disease, measure the extent of emphysema and small airways disease in COPD, and detect concomitant disease, such as asthma, ?brosis, and cardiovascular disease. Some of the main obstacles in using CT imaging to study the lung are associated with achieving reliable lung volumes (levels of inspiration) during scanning, variations in protocols across scans producing changes in measured CT values, and inter-site and inter-manufacturer differences which reduce the reproducibility of scanning in large multi-center trials. The use of CT is further limited by the current practice of using CT density-based thresholds to de?ne the location and extent of disease. We hypothesize that further advances in our understanding of COPD are possible by complementing CT density as the primary image-based indicator of disease with measurements of regional lung mechanics. We propose to study the biomechanics of the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) cohort. We will look for differences in mechanical behavior across the SPIROMICS disease strata, examine the impact of lobar anatomy and ?ssure integrity on lung mechanics and disease distribution, and identify image-based biomarkers that are predictive of COPD progression by analyzing the SPIROMICS data longitudinally. When complete, this project will produce a database describing the biomechanics of the SPIROMICS cohort, identify descriptive biomarkers of COPD for subject phenotyping, and create a disease progression model based on lung biomechanics.